Genetic Variant STAP2:c.1073-103C>A (chr19-4324632-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_017720.3(STAP2):c.1108C>A(p.Leu370Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STAP2
NM_017720.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.799

Variant links:

Genes affected

STAP2 (HGNC:30430): (signal transducing adaptor family member 2) This gene encodes the substrate of breast tumor kinase, an Src-type non-receptor tyrosine kinase. The encoded protein possesses domains and several tyrosine phosphorylation sites characteristic of adaptor proteins that mediate the interactions linking proteins involved in signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

STAP2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077739626).

BP6

Variant 19-4324632-G-T is Benign according to our data. Variant chr19-4324632-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3170927.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAP2	NM_001013841.2 link	c.1073-103C>A		intron_variant	Intron 11 of 12	ENST00000594605.6	NP_001013863.1	Q9UGK3-1
STAP2	NM_017720.3 link	c.1108C>A	p.Leu370Ile	missense_variant	Exon 12 of 13		NP_060190.2	Q9UGK3-2
STAP2	XM_011528123.2 link	c.1105C>A	p.Leu369Ile	missense_variant	Exon 12 of 13		XP_011526425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAP2	ENST00000594605.6 link	c.1073-103C>A		intron_variant	Intron 11 of 12	1	NM_001013841.2	ENSP00000471052.1		Q9UGK3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000188

AC:

AN:

1063440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

533450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000255

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 10, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.23

DANN

Benign

0.87

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.69

M_CAP

Benign

0.0023

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

Sift4G

Uncertain

0.0060

Polyphen

0.0

Vest4

0.10

MutPred

0.47

Loss of glycosylation at S375 (P = 0.1);

MVP

0.18

MPC

0.31

ClinPred

0.037

GERP RS

-0.77

gMVP

0.077

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over